Ecto-5?-nucleotidase (CD73) plays an important role in the development of several types of cancer; however, its prognostic significance in salivary gland tumors remains unknown. The current study was conducted to investigate the expression of CD73 in such tumors. In this retrospective study, immunohistochemical expression of CD73 was evaluated in 25 pleomorphic adenomas, 20 mucoepidermoid carcinomas and 20 adenoid cystic carcinomas using the Envision technique. Labeling indices of CD73 expression were calculated and compared between lesions. Immunohistochemical analysis demonstrated that the CD73 expression was significantly higher in salivary gland tumors than in normal salivary gland tissue (p<0.001). CD73 expression was significantly higher in mucoepidermoid carcinoma and adenoid cystic carcinoma compared to pleomorphic adenoma p<0.001). In addition, the expression of CD73 was significantly higher in lymph node metastasizing cancers compared to non-metastasizing malignancies (P<0.001). In contrast, there was no significant association between CD73 expression and other clinicopathological variables such as age, gender, tumor size and distant metastasis (P>0.05). The findings suggest that CD73 can be an independent and useful biomarker for predicting the clinical behavior of salivary gland tumors.